Mylacand 8 mg, 16 mg Tablet

u2022 MYLACAND is indicated for the treatment of mild to moderate hypertension.

u2022 MYLACAND can be used as monotherapy or in combination with other antihypertensive agents such as thiazide diuretics and dihydropyride calcium antagonists for enhanced efficacy.

u2022 Heart failure: Treatment with MYLACAND reduces mortality, reduces hospitalisation due to heart failure, and improves symptoms in patients with left ventricular systolic dysfunction (LVEF u2264 40 %).

Posology

Dosage in hypertension:

• The recommended initial dose is MYLACAND 8 mg once daily.
• The usual maintenance dose is 8 mg to 16 mg once daily. The maximal antihypertensive effect is attained within 4 weeks of initiation of treatment. Some patients may receive an additional benefit by increasing the dose to 32 mg once daily.

Concomitant therapy:

• MYLACAND can be used as monotherapy or in combination with other antihypertensive agents, such as thiazide diuretics and dihydropyridine calcium antagonists, e.g. amlodipine, for enhanced efficacy.
• MYLACAND can be administered with other heart failure treatment, including ACE inhibitors, beta-blockers, and digoxin or a combination of these medicines (see section 5.1).

Use in black patients:

• The antihypertensive effect of MYLACAND is less in black than non-black (Caucasian, Asian and other) patients.
• Consequently, up titration of MYLACAND and concomitant therapy (such as thiazide diuretics) may be more frequently needed for blood pressure control in black than non-black patients.

Dosage in heart failure:

• The usual recommended initial dose of MYLACAND is 4 mg once daily.
• Up titration to the target dose of 32 mg once daily or the highest tolerated dose is done by doubling the dose at intervals of at least 2 weeks (see section 4.4).

Special populations:

Elderly population:

• No initial dosage adjustment is necessary for elderly patients with normal renal and hepatic function.

Renal impairment:

• No initial dosage adjustment is necessary in patients with mild to moderate renal impairment (i.e. creatinine clearance u2265 30 ml/min/1,73mu00b2 BSA).
• In patients with severe renal impairment (i.e. creatinine clearance < 30 ml/min/1,73mu00b2 BSA), MYLACAND is contraindicated (see section 4.3).

Hepatic Impairment:

• No initial dosage adjustment is necessary in patients with mild to moderate hepatic impairment. There is no experience available in patients with severe hepatic impairment and/or cholestasis (see section 4.3).
• A lower initial dose of 4 mg should be considered.

Paediatric population

• The safety and efficacy of MYLACAND have not been established in children.

Method of administration

• For oral use.
• MYLACAND should be taken once daily with or without food.

• Hypersensitivity to the active substance, candesartan cilexetil or to any of the excipients of MYLACAND.
• A history of angioedema related to previous therapy with ACE inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines.
• Hereditary or idiopathic angioedema.
• Hypertrophic obstructive cardiomyopathy (HOCM) (see section 4.4).
• Severe renal function impairment (creatinine clearance less than 30 ml/min).
• Bilateral renal artery stenosis.
• Renal artery stenosis in patients with a single kidney.
• Aortic stenosis.
• Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride (see section 4.5).
• Porphyria.
• Lithium therapy: Concomitant administration with MYLACAND may lead to toxic blood concentrations of lithium (see section 4.5).
• Pregnancy and lactation (see section 4.6).
• Severe hepatic impairment and/or cholestasis (see section 4.2 sub-header u2018Hepatic Impairmentu2019).
• The concomitant use of MYLACAND with aliskiren-containing products is contraindicated (see section 4.4 & 4.5).
• Concomitant use of fluoroquinolones with ACE inhibitors/Renin-Angiotensin blockers is contraindicated in patients with moderate to severe renal impairment.

Renal impairment: Changes in renal function may be anticipated in susceptible patients treated with MYLACAND. When administering MYLACAND to patients with severe renal impairment, periodic monitoring of serum potassium and creatinine levels should be considered. There is very limited experience in patients with very severe or end-stage renal impairment (creatinine clearance < 30 ml/min/1,73 mu00b2 BSA) (see section 4.3).

Evaluation of patients with heart failure should include periodic assessments of renal function. During dose titration of MYLACAND, monitoring of serum creatinine and potassium is recommended.

Pregnancy: Should a woman become pregnant while receiving MYLACAND, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine (see section 4.3 and 4.6). In post-menarche patients the possibility of pregnancy should be evaluated on a regular basis. Appropriate information should be given and/or action taken to prevent the risk of exposure during pregnancy (see sections 4.3 and 4.6).

Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients (see section 4.3). Renal function should be assessed before initiating treatment, and monitored during treatment, with fluoroquinolones or ACE inhibitors/renin-angiotensin receptor blockers.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers (ARBs) or aliskiren may increase the risk of hypotension, hyperkalaemia and decreases renal function (including acute renal failure). Dual blockade of RAAS through the combined use of MYLACAND and aliskiren is therefore contraindicated (see section 4.3). MYLACAND should not be used concomitantly with aliskiren (see section 4.3).

Hypotension: Hypotension may occur during treatment with MYLACAND in heart failure patients. It may also occur in hypertensive patients with intravascular volume depletion. Caution should be observed when initiating therapy and correction of hypovolaemia should be attempted.

Haemodialysis: During dialysis the blood pressure may be particularly sensitive to AT1-receptor blockade as a result of reduced plasma volume and activation of the renin-angiotensin-aldosterone system. Therefore, candesartan as contained in MYLACAND should be carefully titrated with thorough monitoring of blood pressure in patients on haemodialysis.

Renal artery stenosis: MYLACAND may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney (see section 4.3).

Kidney transplantation: There is no experience regarding the administration of MYLACAND in patients with recent kidney transplantation.

Hepatic impairment: There is no experience in patients with severe hepatic impairment and/or cholestasis.

Aortic and mitral valve stenosis (obstructive hypertrophic cardiomyopathy): MYLACAND is contraindicated in patients suffering from haemodynamically relevant aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy (see section 4.3).

Primary hyperaldosteronism: Patients with primary hyperaldosteronism will not generally respond to antihypertensive medicines acting through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of candesartan is not recommended in this population.

Hyperkalaemia: Concomitant use of MYLACAND with potassium supplements, salt substitutes containing potassium or other medicines that may increase potassium levels (e.g. heparin) may lead to increases in serum potassium in hypertensive patients. Monitoring of potassium should be undertaken as appropriate. In heart failure patients treated with MYLACAND, hyperkalaemia may occur. During treatment with MYLACAND in patients with heart failure, periodic monitoring of serum potassium is recommended, especially when taken concomitantly with ACE inhibitors.

Anaesthesia and surgery: Hypotension may occur during anaesthesia and surgery in patients treated with MYLACAND, due to blockade of the renin-angiotension system. Hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors.

General: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicines that affect this system has been associated with acute hypotension, azotaemia, uraemia, oliguria or rarely, acute renal failure. Excessive blood pressure decreases in patients with ischaemic cardiopathy, or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke.

Lactose warning: MYLACAND contains lactose which may have an effect on the glycaemic control of patients with diabetes mellitus. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take MYLACAND.

• No interactions of clinical significance have been identified.
• Compounds which have been investigated in clinical pharmacokinetic studies include hydrochlorothiazide, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine.
• Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicines (e.g. heparin) may increase potassium levels. Monitoring of potassium should be undertaken as appropriate (see section 4.4).

• Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. A similar effect may occur with MYLACAND (see section 4.3).
• The antihypertensive effect of MYLACAND may be enhanced by other antihypertensive medicines. When MYLACAND is administered simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (i.e. selective COX-2 inhibitors, acetylsalicylic acid and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.
• The bioavailability of candesartan is not affected by food.
• Post marketing reports suggest a rare but significant interaction with increase of INR and bleeding with concomitant warfarin therapy.
• Dual blockade of the RAAS with ARBs, ACE inhibitors, or aliskiren: Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (see section 4.3 & 4.4).
• Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers may precipitate acute kidney injury (see section 4.3).

Women of childbearing potential/ Contraception in males and females: Women of childbearing age should ensure effective contraception.

Pregnancy: Safety in pregnancy and lactation has not been established (see section 4.3). When pregnancy is planned or confirmed MYLACAND should be discontinued. Medicines affecting the renin-angiotensin system, such as MYLACAND, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women.

Breastfeeding: Candesartan is excreted in breast milk. Because of the potential for adverse effects on the breastfed infant, breastfeeding should be discontinued if the use of MYLACAND is considered essential (see section 4.3).

The effect of MYLACAND on the ability to drive and use machines has not been studied. When driving vehicles or operating machines, it should be taken into account that dizziness or weariness may occur during treatment.

MYLACAND can have side effects.

a. Summary of the safety profile: Treatment of Heart Failure: The adverse experience profile of candesartan cilexetil in heart failure patients was consistent with the pharmacology of the substance and the health status of the patients. The most frequently reported adverse reactions were hyperkalaemia, hypotension and renal impairment. These events were more frequent in patients over 70 years of age, diabetics, or subjects who received other medicines.

b. Tabulated list of adverse reactions:

Description of selected adverse reactions: Laboratory findings: Small decreases in haemoglobin have been seen in patients with renal impairment. Periodic monitoring of serum potassium and creatinine levels is recommended.

In overdose, side effects can be precipitated and/or be of increased severity (see section 4.8).

Symptoms: Based on pharmacological considerations, the main manifestation of an overdose is likely to be symptomatic hypotension and dizziness.

Treatment: If symptomatic hypotension should occur, symptomatic treatment should be instituted, and vital signs monitored. The patient should be placed supine with the legs elevated. If this is not sufficient, plasma volume should be increased by infusion of, for example, isotonic saline solution. Sympathomimetic medicines may be administered if the above-mentioned measures are not sufficient.

Note: Candesartan is not removed by haemodialysis.